Precise Targeting of Surgical Photodisruption

ABSTRACT

Techniques, apparatus and systems for laser surgery including imaging-guided surgery techniques, apparatus and systems.

PRIORITY CLAIM AND RELATED PATENT APPLICATION

This document claims priority from and benefit of U.S. PatentApplication No. 60/970,477 entitled “Precise Targeting of SurgicalPhotodisruption” and filed on Sep. 6, 2007, which is incorporated byreference as part of the specification of this document.

BACKGROUND

This document relates to laser surgery techniques, apparatus andsystems, including laser surgery techniques, apparatus and systems basedon photodisruption caused by laser pulses in a tissue.

Laser light can be used to perform various surgical operations in eyesand other tissues in humans and animals. Recent development of lasersurgical methods for performing operations on the human eye, such asLASIK combined with flap creation using a femtosecond laser,demonstrates that surgery of the human eye with lasers often requiresprecision and speed which cannot be achieved by manual and mechanicalsurgical methods. In laser surgery such as laser ophthalmic surgery,laser pulses interact with a target tissue to cause one or more desiredsurgical effects in the tissue. One example of surgical effects is thelaser-induced photodisruption, a nonlinear optical interaction betweenlight and a tissue that causes the tissue to ionize. Laser-inducedphotodisruption can be used to selectively remove or disrupt tissue invarious surgical procedures, such as laser surgery in opthalmology.Traditional ophthalmic photodisruptors have used relatively long pulseduration lasers in single shot or burst modes involving a series ofapproximately a few laser pulses (e.g., three) from a pulsed laser suchas a pulsed Nd:YAG laser. Newer laser surgical systems including laserophthalmic systems tend to operate with short laser pulses with highrepetition rates, e.g., thousands of shots per second and relatively lowenergy per pulse.

One technical challenge associated with surgical lasers of short laserpulses with high repetition rates is precise control and aiming of thelaser pulses, e.g., the beam position and beam focusing of the pulses ina surgical laser beam.

SUMMARY

This document describes implementations of techniques, apparatus andsystems for laser surgery.

In one aspect, a laser surgical system includes a pulse laser to producea laser beam of laser pulses; an optics module to receive the laser beamand to focus and direct the laser beam onto a target tissue to causephotodisruption in the target tissue; an applanation plate operable tobe in contact with the target tissue to produce an interface and totransmit laser pulses to the target and reflected or scattered light orsound from the target through the interface; an imaging device tocapture light or sound from the target to create an image of the targettissue; and a system control module to process imaging information onthe image from the imaging device and to control the optics module toadjust the laser beam focus to the target tissue based on the imaginginformation.

In another aspect, a method for targeting a pulsed laser beam to atarget tissue in laser surgery includes monitoring image of targettissue of a body part and image of a reference on the body part to aimthe pulsed laser beam at the target tissue; and monitoring images ofphotodisruption byproduct and the target tissue to adjust the pulsedlaser beam to overlap the location of the photodisruption byproduct withthe target tissue.

In another aspect, a method for targeting a pulsed laser beam to atarget tissue in laser surgery includes monitoring image of targettissue of a body part and image of a reference on the body part to aimthe pulsed laser beam at the target tissue; obtaining images ofphotodisruption byproduct in a calibration material to generate athree-dimensional reference system inside the target tissue; andcontrolling the focusing and scanning of the surgical laser beam duringthe surgery in the target tissue based on the three-dimensionalreference system.

In another aspect, a method for targeting a pulsed laser beam to atarget tissue in laser surgery includes aiming a pulsed laser beam at atarget tissue location within target tissue to deliver a sequence ofinitial alignment laser pulses to the target tissue location; monitoringimages of the target tissue location and photodisruption byproductcaused by the initial alignment laser pulses to obtain a location of thephotodisruption byproduct relative to the target tissue location;controlling the pulsed laser beam to carry surgical laser pulses at thesurgical pulse energy level; adjusting a position of the pulsed laserbeam at the surgical pulse energy level to place the location ofphotodisruption byproduct at the determined location; and, whilemonitoring images of the target tissue and the photodisruptionbyproduct, continuing to adjust position of the pulsed laser beam at thesurgical pulse energy level to place the location of photodisruptionbyproduct at a respective determined location when moving the pulsedlaser beam to a new target tissue location within the target tissue.

In another aspect, a laser surgical system includes a pulsed laser toproduce a pulsed laser beam; a beam control optical module that directsthe pulsed laser beam at a target tissue location within target tissueto deliver a sequence of initial alignment laser pulses to the targettissue location; a monitor to monitor images of the target tissuelocation and photodisruption byproduct caused by the initial alignmentlaser pulses to obtain a location of the photodisruption byproductrelative to the target tissue location; and a laser control unit thatcontrols a power level of the pulsed laser beam to carry surgical laserpulses at a surgical pulse energy level different from the initialalignment laser pulses and operates the beam control optical module,based on monitored images of the target tissue and the photodisruptionbyproduct from the monitor, to adjust a position of the pulsed laserbeam at the surgical pulse energy level to place the location ofphotodisruption byproduct at a desired location.

In another aspect, a method for performing laser surgery by using animaging-guided laser surgical system includes using an applanation platein the system to engage to and to hold a target tissue under surgery inposition; sequentially or simultaneously directing a surgical laser beamof laser pulses from a laser in the system and an optical probe beamfrom an optical coherence tomography (OCT) module in the system to thepatient interface into the target tissue; controlling the surgical laserbeam to perform laser surgery in the target tissue; operating the OCTmodule to obtain OCT images inside the target tissue from light of theoptical probe beam returning from the target tissue; and applyingposition information in the obtained OCT images in focusing and scanningof the surgical laser beam to dynamically adjust the focusing andscanning of the surgical laser beam in the target tissue before orduring surgery.

In another aspect, a method for performing laser surgery by using animaging-guided laser surgical system includes using an applanation platein the system, to hold a calibration sample material during acalibration process before performing a surgery; directing a surgicallaser beam of laser pulses from a laser in the system to the patientinterface into the calibration sample material to burn reference marksat selected three dimensional reference locations; directing an opticalprobe beam from an optical coherence tomography (OCT) module in thesystem to the patient interface into the calibration sample material tocapture OCT images of the burnt reference marks; establishing arelationship between positioning coordinates of the OCT module and theburnt reference marks; after the establishing the relationship, using apatient interface in the system to engage to and to hold a target tissueunder surgery in position; simultaneously or sequentially directing thesurgical laser beam of laser pulses and the optical probe beam to thepatient interface into the target tissue; controlling the surgical laserbeam to perform laser surgery in the target tissue; operating the OCTmodule to obtain OCT images inside the target tissue from light of theoptical probe beam returning from the target tissue; and applyingposition information in the obtained OCT images and the establishedrelationship in focusing and scanning of the surgical laser beam todynamically adjust the focusing and scanning of the surgical laser beamin the target tissue before or during surgery.

In another aspect, a laser system for performing laser surgery on theeye includes a control system; a laser source emitting a laser beam forsurgically affecting the tissue of an eye under a control of the controlsystem; an optical coherence tomography (OCT) imaging system a controlof the control system to produce a probe light beam that opticallygathers information on an internal structure of the eye; an attachmentmechanism structured to fix the surface of the eye in position and toprovide reference in three dimensional space relative to the OCT imagingsystem; a mechanism to supply the control system with positionalinformation on the internal structure of the eye derived from the OCTimaging system; and an optical unit that focuses the laser beamcontrolled by the control system into the eye for surgical treatment.

In another aspect, An imaging-guided laser surgical system includes asurgical laser that produces a surgical laser beam of surgical laserpulses that cause surgical changes in a target tissue under surgery; apatient interface mount that engages a patient interface in contact withthe target tissue to hold the target tissue in position; a laser beamdelivery module located between the surgical laser and the patientinterface and configured to direct the surgical laser beam to the targettissue through the patient interface, the laser beam delivery moduleoperable to scan the surgical laser beam in the target tissue along apredetermined surgical pattern; a laser control module that controlsoperation of the surgical laser and controls the laser beam deliverymodule to produce the predetermined surgical pattern; and an opticalcoherence tomography (OCT) module positioned relative to the patientinterface to have a known spatial relation with respect to the patientinterface and the target issue fixed to the patient interface. The OCTmodule is configured to direct an optical probe beam to the targettissue and receive returned probe light of the optical probe beam fromthe target tissue to capture OCT images of the target tissue while thesurgical laser beam is being directed to the target tissue to perform ansurgical operation so that the optical probe beam and the surgical laserbeam are simultaneously present in the target tissue, the OCT module incommunication with the laser control module to send information of thecaptured OCT images to the laser control module. The laser controlmodule responds to the information of the captured OCT images to operatethe laser beam delivery module in focusing and scanning of the surgicallaser beam and adjusts the focusing and scanning of the surgical laserbeam in the target tissue based on positioning information in thecaptured OCT images.

In another aspect, a laser system includes a pulse laser to produce alaser beam of laser pulses; an optics module to receive the laser beamand to focus and direct the laser beam onto a target tissue to causephotodisruption in the target tissue; an applanation plate operable tobe in contact with the target tissue to produce an interface and totransmit laser pulses to the target and reflected light or sound fromthe target through the interface; an imaging device to capture reflectedlight from the target to create an image of the target tissue; and asystem control module to process imaging information on the capturedimages from the image device and to control the optics module to adjustthe laser beam focus to the target tissue.

In another aspect, a laser system includes a pulse laser to produce alaser beam of laser pulses; an optics module to focus and direct thelaser beam onto a target tissue to cause photodisruption in the targettissue; an applanation plate operable to be in contact with the targettissue to produce an interface and to transmit laser pulses to thetarget and reflected light or sound from the target through theinterface; an imaging device to capture an image of the target tissueand an image of the photodisruption byproduct generated in the targettissue by the photodisruption; and a system control module to processimaging information on the captures images from the image device toobtain an offset in position between the image of the photodisruptionbyproduct and a targeted position in the target tissue, wherein thesystem control module operates to control the optics module to adjustthe laser beam to reduce the offset in subsequent laser pulses.

In another aspect, a method for targeting a pulsed laser beam to atarget tissue in laser surgery includes monitoring image of targettissue of a body part and image of a reference on the body part to aimthe pulsed laser beam at the target tissue; and monitoring images ofphotodisruption byproduct and the target tissue to adjust the pulsedlaser beam to overlap the location of the photodisruption byproduct withthe target tissue.

In another aspect, a method for targeting a pulsed laser beam to atarget tissue in laser surgery includes aiming a pulsed laser beam at atarget tissue location within target tissue to deliver a sequence ofinitial alignment laser pulses to the target tissue location; monitoringimages of the target tissue location and photodisruption byproductcaused by the initial alignment laser pulses to obtain a location of thephotodisruption byproduct relative to the target tissue location;determining a location of photodisruption byproduct caused by surgicallaser pulses at a surgical pulse energy level different from the initialalignment laser pulses when the pulsed laser beam of the surgical laserpulses is placed at the target tissue location; controlling the pulsedlaser beam to carry surgical laser pulses at the surgical pulse energylevel; adjusting a position of the pulsed laser beam at the surgicalpulse energy level to place the location of photodisruption byproduct atthe determined location; and, while monitoring images of the targettissue and the photodisruption byproduct, continuing to adjust positionof the pulsed laser beam at the surgical pulse energy level to place thelocation of photodisruption byproduct at a respective determinedlocation when moving the pulsed laser beam to a new target tissuelocation within the target tissue.

In yet another aspect, a laser surgical system includes a pulsed laserto produce a pulsed laser beam; a beam control optical module thatdirects the pulsed laser beam at a target tissue location within targettissue to deliver a sequence of initial alignment laser pulses to thetarget tissue location; a monitor to monitor images of the target tissuelocation and photodisruption byproduct caused by the initial alignmentlaser pulses to obtain a location of the photodisruption byproductrelative to the target tissue location; and a laser control unit thatcontrols a power level of the pulsed laser beam to carry surgical laserpulses at a surgical pulse energy level different from the initialalignment laser pulses and operates the beam control optical module,based on monitored images of the target tissue and the photodisruptionbyproduct from the monitor, to adjust a position of the pulsed laserbeam at the surgical pulse energy level to place the location ofphotodisruption byproduct at a desired location.

These and other aspects and various implementations of techniques,apparatus and systems for laser surgery are described in detail in thedrawings, the description and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of an imaging-guided laser surgical system inwhich an imaging module is provided to provide imaging of a target tothe laser control.

FIGS. 2-10 show examples of imaging-guided laser surgical systems withvarying degrees of integration of a laser surgical system and an imagingsystem.

FIG. 11 shows an example of a method for performing laser surgery bysuing an imaging-guided laser surgical system.

FIG. 12 shows an example of an image of an eye from an optical coherencetomography (OCT) imaging module.

FIGS. 13A, 13B, 13C and 13D show two examples of calibration samples forcalibrating an imaging-guided laser surgical system.

FIG. 14 shows an example of attaching a calibration sample material to apatient interface in an imaging-guided laser surgical system forcalibrating the system.

FIG. 15 shows an example of reference marks created by a surgical laserbeam on a glass surface.

FIG. 16 shows an example of the calibration process and thepost-calibration surgical operation for an imaging-guided laser surgicalsystem.

FIGS. 17 A and 17B show two operation modes of an exemplaryimaging-guided laser surgical system that captures images oflaser-induced photodisruption byproduct and the target issue to guidelaser alignment.

FIGS. 18 and 19 show examples of laser alignment operations inimaging-guided laser surgical systems.

FIG. 20 shows an exemplary laser surgical system based on the laseralignment using the image of the photodisruption byproduct.

DETAILED DESCRIPTION

One important aspect of laser surgical procedures is precise control andaiming of a laser beam, e.g., the beam position and beam focusing. Lasersurgery systems can be designed to include laser control and aimingtools to precisely target laser pulses to a particular target inside thetissue. In various nanosecond photodisruptive laser surgical systems,such as the Nd:YAG laser systems, the required level of targetingprecision is relatively low. This is in part because the laser energyused is relatively high and thus the affected tissue area is alsorelatively large, often covering an impacted area with a dimension inthe hundreds of microns. The time between laser pulses in such systemstend to be long and manual controlled targeting is feasible and iscommonly used. One example of such manual targeting mechanisms is abiomicroscope to visualize the target tissue in combination with asecondary laser source used as an aiming beam. The surgeon manuallymoves the focus of a laser focusing lens, usually with a joystickcontrol, which is parfocal (with or without an offset) with their imagethrough the microscope, so that the surgical beam or aiming beam is inbest focus on the intended target.

Such techniques designed for use with low repetition rate laser surgicalsystems may be difficult to use with high repetition rate lasersoperating at thousands of shots per second and relatively low energy perpulse. In surgical operations with high repetition rate lasers, muchhigher precision may be required due to the small effects of each singlelaser pulse and much higher positioning speed may be required due to theneed to deliver thousands of pulses to new treatment areas very quickly.

Examples of high repetition rate pulsed lasers for laser surgicalsystems include pulsed lasers at a pulse repetition rate of thousands ofshots per second or higher with relatively low energy per pulse. Suchlasers use relatively low energy per pulse to localize the tissue effectcaused by laser-induced photodisruption, e.g., the impacted tissue areaby photodisruption on the order of microns or tens of microns. Thislocalized tissue effect can improve the precision of the laser surgeryand can be desirable in certain surgical procedures such as laser eyesurgery. In one example of such surgery, placement of many hundred,thousands or millions of contiguous, nearly contiguous or pulsesseparated by known distances, can be used to achieve certain desiredsurgical effects, such as tissue incisions, separations orfragmentation.

Various surgical procedures using high repetition rate photodisruptivelaser surgical systems with shorter laser pulse durations may requirehigh precision in positioning each pulse in the target tissue undersurgery both in an absolute position with respect to a target locationon the target tissue and a relative position with respect to precedingpulses. For example, in some cases, laser pulses may be required to bedelivered next to each other with an accuracy of a few microns withinthe time between pulses, which can be on the order of microseconds.Because the time between two sequential pulses is short and theprecision requirement for the pulse alignment is high, manual targetingas used in low repetition rate pulsed laser systems may be no longeradequate or feasible.

One technique to facilitate and control precise, high speed positioningrequirement for delivery of laser pulses into the tissue is attaching aapplanation plate made of a transparent material such as a glass with apredefined contact surface to the tissue so that the contact surface ofthe applanation plate forms a well-defined optical interface with thetissue. This well-defined interface can facilitate transmission andfocusing of laser light into the tissue to control or reduce opticalaberrations or variations (such as due to specific eye opticalproperties or changes that occur with surface drying) that are mostcritical at the air-tissue interface, which in the eye is at theanterior surface of the cornea. Contact lenses can be designed forvarious applications and targets inside the eye and other tissues,including ones that are disposable or reusable. The contact glass orapplanation plate on the surface of the target tissue can be used as areference plate relative to which laser pulses are focused through theadjustment of focusing elements within the laser delivery system. Thisuse of a contact glass or applanation plate provides better control ofthe optical qualities of the tissue surface and thus allow laser pulsesto be accurately placed at a high speed at a desired location(interaction point) in the target tissue relative to the applanationplate with little optical distortion of the laser pulses.

One way for implementing an applanation plate on an eye is to use theapplanation plate to provide a positional reference for delivering thelaser pulses into a target tissue in the eye. This use of theapplanation plate as a positional reference can be based on the knowndesired location of laser pulse focus in the target with sufficientaccuracy prior to firing the laser pulses and that the relativepositions of the reference plate and the individual internal tissuetarget must remain constant during laser firing. In addition, thismethod can require the focusing of the laser pulse to the desiredlocation to be predictable and repeatable between eyes or in differentregions within the same eye. In practical systems, it can be difficultto use the applanation plate as a positional reference to preciselylocalize laser pulses intraocularly because the above conditions may notbe met in practical systems.

For example, if the crystalline lens is the surgical target, the precisedistance from the reference plate on the surface of the eye to thetarget tends to vary due to the presence of a collapsible structures,such as the cornea itself, the anterior chamber, and the iris. Not onlyis their considerable variability in the distance between the applanatedcornea and the lens between individual eyes, but there can also bevariation within the same eye depending on the specific surgical andapplanation technique used by the surgeon. In addition, there can bemovement of the targeted lens tissue relative to the applanated surfaceduring the firing of the thousands of laser pulses required forachieving the surgical effect, further complicating the accuratedelivery of pulses. In addition, structure within the eye may move dueto the build-up of photodisruptive byproducts, such as cavitationbubbles. For example, laser pulses delivered to the crystalline lens cancause the lens capsule to bulge forward, requiring adjustment to targetthis tissue for subsequent placement of laser pulses. Furthermore, itcan be difficult to use computer models and simulations to predict, withsufficient accuracy, the actual location of target tissues after theapplanation plate is removed and to adjust placement of laser pulses toachieve the desired localization without applanation in part because ofthe highly variable nature of applanation effects, which can depend onfactors particular to the individual cornea or eye, and the specificsurgical and applanation technique used by a surgeon.

In addition to the physical effects of applanation thatdisproportionably affect the localization of internal tissue structures,in some surgical processes, it may be desirable for a targeting systemto anticipate or account for nonlinear characteristics ofphotodisruption which can occur when using short pulse duration lasers.Photodisruption is a nonlinear optical process in the tissue materialand can cause complications in beam alignment and beam targeting. Forexample, one of the nonlinear optical effects in the tissue materialwhen interacting with laser pulses during the photodisruption is thatthe refractive index of the tissue material experienced by the laserpulses is no longer a constant but varies with the intensity of thelight. Because the intensity of the light in the laser pulses variesspatially within the pulsed laser beam, along and across the propagationdirection of the pulsed laser beam, the refractive index of the tissuematerial also varies spatially. One consequence of this nonlinearrefractive index is self-focusing or self-defocusing in the tissuematerial that changes the actual focus of and shifts the position of thefocus of the pulsed laser beam inside the tissue. Therefore, a precisealignment of the pulsed laser beam to each target tissue position in thetarget tissue may also need to account for the nonlinear optical effectsof the tissue material on the laser beam. In addition, it may benecessary to adjust the energy in each pulse to deliver the samephysical effect in different regions of the target due to differentphysical characteristics, such as hardness, or due to opticalconsiderations such as absorption or scattering of laser pulse lighttraveling to a particular region. In such cases, the differences innon-linear focusing effects between pulses of different energy valuescan also affect the laser alignment and laser targeting of the surgicalpulses.

Thus, in surgical procedures in which non superficial structures aretargeted, the use of a superficial applanation plate based on apositional reference provided by the applanation plate may beinsufficient to achieve precise laser pulse localization in internaltissue targets. The use of the applanation plate as the reference forguiding laser delivery may require measurements of the thickness andplate position of the applanation plate with high accuracy because thedeviation from nominal is directly translated into a depth precisionerror. High precision applanation lenses can be costly, especially forsingle use disposable applanation plates.

The techniques, apparatus and systems described in this document can beimplemented in ways that provide a targeting mechanism to deliver shortlaser pulses through an applanation plate to a desired localizationinside the eye with precision and at a high speed without requiring theknown desired location of laser pulse focus in the target withsufficient accuracy prior to firing the laser pulses and withoutrequiring that the relative positions of the reference plate and theindividual internal tissue target remain constant during laser firing.As such, the present techniques, apparatus and systems can be used forvarious surgical procedures where physical conditions of the targettissue under surgery tend to vary and are difficult to control and thedimension of the applanation lens tends to vary from one lens toanother. The present techniques, apparatus and systems may also be usedfor other surgical targets where distortion or movement of the surgicaltarget relative to the surface of the structure is present or non-linearoptical effects make precise targeting problematic. Examples for suchsurgical targets different from the eye include the heart, deeper tissuein the skin and others.

The present techniques, apparatus and systems can be implemented in waysthat maintain the benefits provided by an applanation plate, including,for example, control of the surface shape and hydration, as well asreductions in optical distortion, while providing for the preciselocalization of photodisruption to internal structures of the applanatedsurface. This can be accomplished through the use of an integratedimaging device to localize the target tissue relative to the focusingoptics of the delivery system. The exact type of imaging device andmethod can vary and may depend on the specific nature of the target andthe required level of precision.

An applanation lens may be implemented with another mechanism to fix theeye to prevent translational and rotational movement of the eye.Examples of such fixation devices include the use of a suction ring.Such fixation mechanism can also lead to unwanted distortion or movementof the surgical target. The present techniques, apparatus and systemscan be implemented to provide, for high repetition rate laser surgicalsystems that utilize an applanation plate and/or fixation means fornon-superficial surgical targets, a targeting mechanism to provideintraoperative imaging to monitor such distortion and movement of thesurgical target.

Specific examples of laser surgical techniques, apparatus and systemsare described below to use an optical imaging module to capture imagesof a target tissue to obtain positioning information of the targettissue, e.g., before and during a surgical procedure. Such obtainedpositioning information can be used to control the positioning andfocusing of the surgical laser beam in the target tissue to provideaccurate control of the placement of the surgical laser pulses in highrepetition rate laser systems. In one implementation, during a surgicalprocedure, the images obtained by the optical imaging module can be usedto dynamically control the position and focus of the surgical laserbeam. In addition, lower energy and shot laser pulses tend to besensitive to optical distortions, such a laser surgical system canimplement an applanation plate with a flat or curved interface attachingto the target tissue to provide a controlled and stable opticalinterface between the target tissue and the surgical laser system and tomitigate and control optical aberrations at the tissue surface.

As an example, FIG. 1 shows a laser surgical system based on opticalimaging and applanation. This system includes a pulsed laser 1010 toproduce a surgical laser beam 1012 of laser pulses, and an optics module1020 to receive the surgical laser beam 1012 and to focus and direct thefocused surgical laser beam 1022 onto a target tissue 1001, such as aneye, to cause photodisruption in the target tissue 1001. An applanationplate can be provided to be in contact with the target tissue 1001 toproduce an interface for transmitting laser pulses to the target tissue1001 and light coming from the target tissue 1001 through the interface.Notably, an optical imaging device 1030 is provided to capture light1050 carrying target tissue images 1050 or imaging information from thetarget tissue 1001 to create an image of the target tissue 1001. Theimaging signal 1032 from the imaging device 1030 is sent to a systemcontrol module 1040. The system control module 1040 operates to processthe captured images from the image device 1030 and to control the opticsmodule 1020 to adjust the position and focus of the surgical laser beam1022 at the target tissue 101 based on information from the capturedimages. The optics module 120 can include one or more lenses and mayfurther include one or more reflectors. A control actuator can beincluded in the optics module 1020 to adjust the focusing and the beamdirection in response to a beam control signal 1044 from the systemcontrol module 1040. The control module 1040 can also control the pulsedlaser 1010 via a laser control signal 1042.

The optical imaging device 1030 may be implemented to produce an opticalimaging beam that is separate from the surgical laser beam 1022 to probethe target tissue 1001 and the returned light of the optical imagingbeam is captured by the optical imaging device 1030 to obtain the imagesof the target tissue 1001. One example of such an optical imaging device1030 is an optical coherence tomography (OCT) imaging module which usestwo imaging beams, one probe beam directed to the target tissue 1001thought the applanation plate and another reference beam in a referenceoptical path, to optically interfere with each other to obtain images ofthe target tissue 1001. In other implementations, the optical imagingdevice 1030 can use scattered or reflected light from the target tissue1001 to capture images without sending a designated optical imaging beamto the target tissue 1001. For example, the imaging device 1030 can be asensing array of sensing elements such as CCD or CMS sensors. Forexample, the images of photodisruption byproduct produced by thesurgical laser beam 1022 may be captured by the optical imaging device1030 for controlling the focusing and positioning of the surgical laserbeam 1022. When the optical imaging device 1030 is designed to guidesurgical laser beam alignment using the image of the photodisruptionbyproduct, the optical imaging device 1030 captures images of thephotodisruption byproduct such as the laser-induced bubbles or cavities.The imaging device 1030 may also be an ultrasound imaging device tocapture images based on acoustic images.

The system control module 1040 processes image data from the imagingdevice 1030 that includes the position offset information for thephotodisruption byproduct from the target tissue position in the targettissue 1001. Based on the information obtained from the image, the beamcontrol signal 1044 is generated to control the optics module 1020 whichadjusts the laser beam 1022. A digital processing unit can be includedin the system control module 1040 to perform various data processing forthe laser alignment.

The above techniques and systems can be used deliver high repetitionrate laser pulses to subsurface targets with a precision required forcontiguous pulse placement, as needed for cutting or volume disruptionapplications. This can be accomplished with or without the use of areference source on the surface of the target and can take into accountmovement of the target following applanation or during placement oflaser pulses.

The applanation plate in the present systems is provided to facilitateand control precise, high speed positioning requirement for delivery oflaser pulses into the tissue. Such an applanation plate can be made of atransparent material such as a glass with a predefined contact surfaceto the tissue so that the contact surface of the applanation plate formsa well-defined optical interface with the tissue. This well-definedinterface can facilitate transmission and focusing of laser light intothe tissue to control or reduce optical aberrations or variations (suchas due to specific eye optical properties or changes that occur withsurface drying) that are most critical at the air-tissue interface,which in the eye is at the anterior surface of the cornea. A number ofcontact lenses have been designed for various applications and targetsinside the eye and other tissues, including ones that are disposable orreusable. The contact glass or applanation plate on the surface of thetarget tissue is used as a reference plate relative to which laserpulses are focused through the adjustment of focusing elements withinthe laser delivery system relative. Inherent in such an approach are theadditional benefits afforded by the contact glass or applanation platedescribed previously, including control of the optical qualities of thetissue surface. Accordingly, laser pulses can be accurately placed at ahigh speed at a desired location (interaction point) in the targettissue relative to the applanation plate with little optical distortionof the laser pulses.

The optical imaging device 1030 in FIG. 1 captures images of the targettissue 1001 via the applanation plate. The control module 1040 processesthe captured images to extract position information from the capturedimages and uses the extracted position information as a positionreference or guide to control the position and focus of the surgicallaser beam 1022. This imaging-guided laser surgery can be implementedwithout relying on the applanation plate as a position reference becausethe position of the applanation plate tends to change due to variousfactors as discussed above. Hence, although the applanation plateprovides a desired optical interface for the surgical laser beam toenter the target tissue and to capture images of the target tissue, itmay be difficult to use the applanation plate as a position reference toalign and control the position and focus of the surgical laser beam foraccurate delivery of laser pulses. The imaging-guided control of theposition and focus of the surgical laser beam based on the imagingdevice 1030 and the control module 1040 allows the images of the targettissue 1001, e.g., images of inner structures of an eye, to be used asposition references, without using the applanation plate to provide aposition reference.

In addition to the physical effects of applanation thatdisproportionably affect the localization of internal tissue structures,in some surgical processes, it may be desirable for a targeting systemto anticipate or account for nonlinear characteristics ofphotodisruption which can occur when using short pulse duration lasers.Photodisruption can cause complications in beam alignment and beamtargeting. For example, one of the nonlinear optical effects in thetissue material when interacting with laser pulses during thephotodisruption is that the refractive index of the tissue materialexperienced by the laser pulses is no longer a constant but varies withthe intensity of the light. Because the intensity of the light in thelaser pulses varies spatially within the pulsed laser beam, along andacross the propagation direction of the pulsed laser beam, therefractive index of the tissue material also varies spatially. Oneconsequence of this nonlinear refractive index is self-focusing orself-defocusing in the tissue material that changes the actual focus ofand shifts the position of the focus of the pulsed laser beam inside thetissue. Therefore, a precise alignment of the pulsed laser beam to eachtarget tissue position in the target tissue may also need to account forthe nonlinear optical effects of the tissue material on the laser beam.The energy of the laser pulses may be adjusted to deliver the samephysical effect in different regions of the target due to differentphysical characteristics, such as hardness, or due to opticalconsiderations such as absorption or scattering of laser pulse lighttraveling to a particular region. In such cases, the differences innon-linear focusing effects between pulses of different energy valuescan also affect the laser alignment and laser targeting of the surgicalpulses. In this regard, the direct images obtained from the target issueby the imaging device 1030 can be used to monitor the actual position ofthe surgical laser beam 1022 which reflects the combined effects ofnonlinear optical effects in the target tissue and provide positionreferences for control of the beam position and beam focus.

The techniques, apparatus and systems described here can be used incombination of an applanation plate to provide control of the surfaceshape and hydration, to reduce optical distortion, and provide forprecise localization of photodisruption to internal structures throughthe applanated surface. The imaging-guided control of the beam positionand focus described here can be applied to surgical systems andprocedures that use means other than applanation plates to fix the eye,including the use of a suction ring which can lead to distortion ormovement of the surgical target.

The following sections first describe examples of techniques, apparatusand systems for automated imaging-guided laser surgery based on varyingdegrees of integration of imaging functions into the laser control partof the systems. An optical or other modality imaging module, such as anOCT imaging module, can be used to direct a probe light or other type ofbeam to capture images of a target tissue, e.g., structures inside aneye. A surgical laser beam of laser pulses such as femtosecond orpicosecond laser pulses can be guided by position information in thecaptured images to control the focusing and positioning of the surgicallaser beam during the surgery. Both the surgical laser beam and theprobe light beam can be sequentially or simultaneously directed to thetarget tissue during the surgery so that the surgical laser beam can becontrolled based on the captured images to ensure precision and accuracyof the surgery.

Such imaging-guided laser surgery can be used to provide accurate andprecise focusing and positioning of the surgical laser beam during thesurgery because the beam control is based on images of the target tissuefollowing applanation or fixation of the target tissue, either justbefore or nearly simultaneously with delivery of the surgical pulses.Notably, certain parameters of the target tissue such as the eyemeasured before the surgery may change during the surgery due to variousfactor such as preparation of the target tissue (e.g., fixating the eyeto an applanation lens) and the alternation of the target tissue by thesurgical operations. Therefore, measured parameters of the target tissueprior to such factors and/or the surgery may no longer reflect thephysical conditions of the target tissue during the surgery. The presentimaging-guided laser surgery can mitigate technical issues in connectionwith such changes for focusing and positioning the surgical laser beambefore and during the surgery.

The present imaging-guided laser surgery may be effectively used foraccurate surgical operations inside a target tissue. For example, whenperforming laser surgery inside the eye, laser light is focused insidethe eye to achieve optical breakdown of the targeted tissue and suchoptical interactions can change the internal structure of the eye. Forexample, the crystalline lens can change its position, shape, thicknessand diameter during accommodation, not only between prior measurementand surgery but also during surgery. Attaching the eye to the surgicalinstrument by mechanical means can change the shape of the eye in a notwell defined way and further, the change can vary during surgery due tovarious factors, e.g., patient movement. Attaching means includefixating the eye with a suction ring and aplanating the eye with a flator curved lens. These changes amount to as much as a few millimeters.Mechanically referencing and fixating the surface of the eye such as theanterior surface of the cornea or limbus does not work well whenperforming precision laser microsurgery inside the eye.

The post preparation or near simultaneous imaging in the presentimaging-guided laser surgery can be used to establish three-dimensionalpositional references between the inside features of the eye and thesurgical instrument in an environment where changes occur prior to andduring surgery. The positional reference information provided by theimaging prior to applanation and/or fixation of the eye, or during theactual surgery reflects the effects of changes in the eye and thusprovides an accurate guidance to focusing and positioning of thesurgical laser beam. A system based on the present imaging-guided lasersurgery can be configured to be simple in structure and cost efficient.For example, a portion of the optical components associated with guidingthe surgical laser beam can be shared with optical components forguiding the probe light beam for imaging the target tissue to simplifythe device structure and the optical alignment and calibration of theimaging and surgical light beams.

The imaging-guided laser surgical systems described below use the OCTimaging as an example of an imaging instrument and other non-OCT imagingdevices may also be used to capture images for controlling the surgicallasers during the surgery. As illustrated in the examples below,integration of the imaging and surgical subsystems can be implemented tovarious degrees. In the simplest form without integrating hardware, theimaging and laser surgical subsystems are separated and can communicateto one another through interfaces. Such designs can provide flexibilityin the designs of the two subsystems. Integration between the twosubsystems, by some hardware components such as a patient interface,further expands the functionality by offering better registration ofsurgical area to the hardware components, more accurate calibration andmay improve workflow. As the degree of integration between the twosubsystems increases, such a system may be made increasinglycost-efficient and compact and system calibration will be furthersimplified and more stable over time. Examples for imaging-guided lasersystems in FIGS. 2-10 are integrated at various degrees of integration.

One implementation of a present imaging-guided laser surgical system,for example, includes a surgical laser that produces a surgical laserbeam of surgical laser pulses that cause surgical changes in a targettissue under surgery; a patient interface mount that engages a patientinterface in contact with the target tissue to hold the target tissue inposition; and a laser beam delivery module located between the surgicallaser and the patient interface and configured to direct the surgicallaser beam to the target tissue through the patient interface. Thislaser beam delivery module is operable to scan the surgical laser beamin the target tissue along a predetermined surgical pattern. This systemalso includes a laser control module that controls operation of thesurgical laser and controls the laser beam delivery module to producethe predetermined surgical pattern and an OCT module positioned relativeto the patient interface to have a known spatial relation with respectto the patient interface and the target issue fixed to the patientinterface. The OCT module is configured to direct an optical probe beamto the target tissue and receive returned probe light of the opticalprobe beam from the target tissue to capture OCT images of the targettissue while the surgical laser beam is being directed to the targettissue to perform an surgical operation so that the optical probe beamand the surgical laser beam are simultaneously present in the targettissue. The OCT module is in communication with the laser control moduleto send information of the captured OCT images to the laser controlmodule.

In addition, the laser control module in this particular system respondsto the information of the captured OCT images to operate the laser beamdelivery module in focusing and scanning of the surgical laser beam andadjusts the focusing and scanning of the surgical laser beam in thetarget tissue based on positioning information in the captured OCTimages.

In some implementations, acquiring a complete image of a target tissuemay not be necessary for registering the target to the surgicalinstrument and it may be sufficient to acquire a portion of the targettissue, e.g., a few points from the surgical region such as natural orartificial landmarks. For example, a rigid body has 6 degrees of freedomin 3D space and six independent points would be sufficient to define therigid body. When the exact size of the surgical region is not known,additional points are needed to provide the positional reference. Inthis regard, several points can be used to determine the position andthe curvature of the anterior and posterior surfaces, which are normallydifferent, and the thickness and diameter of the crystalline lens of thehuman eye. Based on these data a body made up from two halves ofellipsoid bodies with given parameters can approximate and visualize acrystalline lens for practical purposes. In another implementation,information from the captured image may be combined with informationfrom other sources, such as pre-operative measurements of lens thicknessthat are used as an input for the controller.

FIG. 2 shows one example of an imaging-guided laser surgical system withseparated laser surgical system 2100 and imaging system 2200. The lasersurgical system 2100 includes a laser engine 2130 with a surgical laserthat produces a surgical laser beam 2160 of surgical laser pulses. Alaser beam delivery module 2140 is provided to direct the surgical laserbeam 2160 from the laser engine 2130 to the target tissue 1001 through apatient interface 2150 and is operable to scan the surgical laser beam2160 in the target tissue 1001 along a predetermined surgical pattern. Alaser control module 2120 is provided to control the operation of thesurgical laser in the laser engine 2130 via a communication channel 2121and controls the laser beam delivery module 2140 via a communicationchannel 2122 to produce the predetermined surgical pattern. A patientinterface mount is provided to engage the patient interface 2150 incontact with the target tissue 1001 to hold the target tissue 1001 inposition. The patient interface 2150 can be implemented to include acontact lens or applanation lens with a flat or curved surface toconformingly engage to the anterior surface of the eye and to hold theeye in position.

The imaging system 2200 in FIG. 2 can be an OCT module positionedrelative to the patient interface 2150 of the surgical system 2100 tohave a known spatial relation with respect to the patient interface 2150and the target issue 1001 fixed to the patient interface 2150. This OCTmodule 2200 can be configured to have its own patient interface 2240 forinteracting with the target tissue 1001. The imaging system 220 includesan imaging control module 2220 and an imaging sub-system 2230. Thesub-system 2230 includes a light source for generating imaging beam 2250for imaging the target 1001 and an imaging beam delivery module todirect the optical probe beam or imaging beam 2250 to the target tissue1001 and receive returned probe light 2260 of the optical imaging beam2250 from the target tissue 1001 to capture OCT images of the targettissue 1001. Both the optical imaging beam 2250 and the surgical beam2160 can be simultaneously directed to the target tissue 1001 to allowfor sequential or simultaneous imaging and surgical operation.

As illustrated in FIG. 2, communication interfaces 2110 and 2210 areprovided in both the laser surgical system 2100 and the imaging system2200 to facilitate the communications between the laser control by thelaser control module 2120 and imaging by the imaging system 2200 so thatthe OCT module 2200 can send information of the captured OCT images tothe laser control module 2120. The laser control module 2120 in thissystem responds to the information of the captured OCT images to operatethe laser beam delivery module 2140 in focusing and scanning of thesurgical laser beam 2160 and dynamically adjusts the focusing andscanning of the surgical laser beam 2160 in the target tissue 1001 basedon positioning information in the captured OCT images. The integrationbetween the laser surgical system 2100 and the imaging system 2200 ismainly through communication between the communication interfaces 2110and 2210 at the software level.

In this and other examples, various subsystems or devices may also beintegrated. For example, certain diagnostic instruments such aswavefront aberrometers, corneal topography measuring devices may beprovided in the system, or pre-operative information from these devicescan be utilized to augment intra-operative imaging.

FIG. 3 shows an example of an imaging-guided laser surgical system withadditional integration features. The imaging and surgical systems sharea common patient interface 3300 which immobilizes target tissue 1001(e.g., the eye) without having two separate patient interfaces as inFIG. 2. The surgical beam 3210 and the imaging beam 3220 are combined atthe patient interface 330 and are directed to the target 1001 by thecommon patient interface 3300. In addition, a common control module 3100is provided to control both the imaging sub-system 2230 and the surgicalpart (the laser engine 2130 and the beam delivery system 2140). Thisincreased integration between imaging and surgical parts allows accuratecalibration of the two subsystems and the stability of the position ofthe patient and surgical volume. A common housing 3400 is provided toenclose both the surgical and imaging subsystems. When the two systemsare not integrated into a common housing, the common patient interface3300 can be part of either the imaging or the surgical subsystem.

FIG. 4 shows an example of an imaging-guided laser surgical system wherethe laser surgical system and the imaging system share both a commonbeam delivery module 4100 and a common patient interface 4200. Thisintegration further simplifies the system structure and system controloperation.

In one implementation, the imaging system in the above and otherexamples can be an optical computed tomography (OCT) system and thelaser surgical system is a femtosecond or picosecond laser basedophthalmic surgical system. In OCT, light from a low coherence,broadband light source such as a super luminescent diode is split intoseparate reference and signal beams. The signal beam is the imaging beamsent to the surgical target and the returned light of the imaging beamis collected and recombined coherently with the reference beam to forman interferometer. Scanning the signal beam perpendicularly to theoptical axis of the optical train or the propagation direction of thelight provides spatial resolution in the x-y direction while depthresolution comes from extracting differences between the path lengths ofthe reference arm and the returned signal beam in the signal arm of theinterferometer. While the x-y scanner of different OCT implementationsare essentially the same, comparing the path lengths and getting z-scaninformation can happen in different ways. In one implementation known asthe time domain OCT, for example, the reference arm is continuouslyvaried to change its path length while a photodetector detectsinterference modulation in the intensity of the re-combined beam. In adifferent implementation, the reference arm is essentially static andthe spectrum of the combined light is analyzed for interference. TheFourier transform of the spectrum of the combined beam provides spatialinformation on the scattering from the interior of the sample. Thismethod is known as the spectral domain or Fourier OCT method. In adifferent implementation known as a frequency swept OCT (S. R. Chinn,et. Al. Opt. Lett. 22 (1997), a narrowband light source is used with itsfrequency swept rapidly across a spectral range. Interference betweenthe reference and signal arms is detected by a fast detector and dynamicsignal analyzer. An external cavity tuned diode laser or frequency tunedof frequency domain mode-locked (FDML) laser developed for this purpose(R. Huber et. Al. Opt. Express, 13, 2005) (S. H. Yun, IEEE J. of Sel. Q.El. 3(4) p. 1087-1096, 1997) can be used in these examples as a lightsource. A femtosecond laser used as a light source in an OCT system canhave sufficient bandwidth and can provide additional benefits ofincreased signal to noise ratios.

The OCT imaging device in the systems in this document can be used toperform various imaging functions. For example, the OCT can be used tosuppress complex conjugates resulting from the optical configuration ofthe system or the presence of the applanation plate, capture OCT imagesof selected locations inside the target tissue to providethree-dimensional positioning information for controlling focusing andscanning of the surgical laser beam inside the target tissue, or captureOCT images of selected locations on the surface of the target tissue oron the applanation plate to provide positioning registration forcontrolling changes in orientation that occur with positional changes ofthe target, such as from upright to supine. The OCT can be calibrated bya positioning registration process based on placement of marks ormarkers in one positional orientation of the target that can then bedetected by the OCT module when the target is in another positionalorientation. In other implementations, the OCT imaging system can beused to produce a probe light beam that is polarized to optically gatherthe information on the internal structure of the eye. The laser beam andthe probe light beam may be polarized in different polarizations. TheOCT can include a polarization control mechanism that controls the probelight used for said optical tomography to polarize in one polarizationwhen traveling toward the eye and in a different polarization whentraveling away from the eye. The polarization control mechanism caninclude, e.g., a wave-plate or a Faraday rotator.

The system in FIG. 4 is shown as a spectral OCT configuration and can beconfigured to share the focusing optics part of the beam delivery modulebetween the surgical and the imaging systems. The main requirements forthe optics are related to the operating wavelength, image quality,resolution, distortion etc. The laser surgical system can be afemtosecond laser system with a high numerical aperture system designedto achieve diffraction limited focal spot sizes, e.g., about 2 to 3micrometers. Various femtosecond ophthalmic surgical lasers can operateat various wavelengths such as wavelengths of around 1.05 micrometer.The operating wavelength of the imaging device can be selected to beclose to the laser wavelength so that the optics is chromaticallycompensated for both wavelengths. Such a system may include a thirdoptical channel, a visual observation channel such as a surgicalmicroscope, to provide an additional imaging device to capture images ofthe target tissue. If the optical path for this third optical channelshares optics with the surgical laser beam and the light of the OCTimaging device, the shared optics can be configured with chromaticcompensation in the visible spectral band for the third optical channeland the spectral bands for the surgical laser beam and the OCT imagingbeam.

FIG. 5 shows a particular example of the design in FIG. 3 where thescanner 5100 for scanning the surgical laser beam and the beamconditioner 5200 for conditioning (collimating and focusing) thesurgical laser beam are separate from the optics in the OCT imagingmodule 5300 for controlling the imaging beam for the OCT. The surgicaland imaging systems share an objective lens 5600 module and the patientinterface 3300. The objective lens 5600 directs and focuses both thesurgical laser beam and the imaging beam to the patient interface 3300and its focusing is controlled by the control module 3100. Two beamsplitters 5410 and 5420 are provided to direct the surgical and imagingbeams. The beam splitter 5420 is also used to direct the returnedimaging beam back into the OCT imaging module 5300. Two beam splitters5410 and 5420 also direct light from the target 1001 to a visualobservation optics unit 5500 to provide direct view or image of thetarget 1001. The unit 5500 can be a lens imaging system for the surgeonto view the target 1001 or a camera to capture the image or video of thetarget 1001. Various beam splitters can be used, such as dichroic andpolarization beam splitters, optical grating, holographic beam splitteror a combinations of these devices.

In some implementations, the optical components may be appropriatelycoated with antireflection coating for both the surgical and for the OCTwavelength to reduce glare from multiple surfaces of the optical beampath. Reflections would otherwise reduce the throughput of the systemand reduce the signal to noise ratio by increasing background light inthe OCT imaging unit. One way to reduce glare in the OCT is to rotatethe polarization of the return light from the sample by wave-plate ofFaraday isolator placed close to the target tissue and orient apolarizer in front of the OCT detector to preferentially detect lightreturned from the sample and suppress light scattered from the opticalcomponents.

In a laser surgical system, each of the surgical laser and the OCTsystem can have a beam scanner to cover the same surgical region in thetarget tissue. Hence, the beam scanning for the surgical laser beam andthe beam scanning for the imaging beam can be integrated to share commonscanning devices.

FIG. 6 shows an example of such a system in detail. In thisimplementation the x-y scanner 6410 and the z scanner 6420 are shared byboth subsystems. A common control 6100 is provided to control the systemoperations for both surgical and imaging operations. The OCT sub-systemincludes an OCT light source 6200 that produce the imaging light that issplit into an imaging beam and a reference beam by a beam splitter 6210.The imaging beam is combined with the surgical beam at the beam splitter6310 to propagate along a common optical path leading to the target1001. The scanners 6410 and 6420 and the beam conditioner unit 6430 arelocated downstream from the beam splitter 6310. A beam splitter 6440 isused to direct the imaging and surgical beams to the objective lens 5600and the patient interface 3300.

In the OCT sub-system, the reference beam transmits through the beamsplitter 6210 to an optical delay device 620 and is reflected by areturn mirror 6230. The returned imaging beam from the target 1001 isdirected back to the beam splitter 6310 which reflects at least aportion of the returned imaging beam to the beam splitter 6210 where thereflected reference beam and the returned imaging beam overlap andinterfere with each other. A spectrometer detector 6240 is used todetect the interference and to produce OCT images of the target 1001.The OCT image information is sent to the control system 6100 forcontrolling the surgical laser engine 2130, the scanners 6410 and 6420and the objective lens 5600 to control the surgical laser beam. In oneimplementation, the optical delay device 620 can be varied to change theoptical delay to detect various depths in the target tissue 1001.

If the OCT system is a time domain system, the two subsystems use twodifferent z-scanners because the two scanners operate in different ways.In this example, the z scanner of the surgical system operates bychanging the divergence of the surgical beam in the beam conditionerunit without changing the path lengths of the beam in the surgical beampath. On the other hand, the time domain OCT scans the z-direction byphysically changing the beam path by a variable delay or by moving theposition of the reference beam return mirror. After calibration, the twoz-scanners can be synchronized by the laser control module. Therelationship between the two movements can be simplified to a linear orpolynomial dependence, which the control module can handle oralternatively calibration points can define a look-up table to provideproper scaling. Spectral/Fourier domain and frequency swept source OCTdevices have no z-scanner, the length of the reference arm is static.Besides reducing costs, cross calibration of the two systems will berelatively straightforward. There is no need to compensate fordifferences arising from image distortions in the focusing optics orfrom the differences of the scanners of the two systems since they areshared.

In practical implementations of the surgical systems, the focusingobjective lens 5600 is slidably or movably mounted on a base and theweight of the objective lens is balanced to limit the force on thepatient's eye. The patient interface 3300 can include an applanationlens attached to a patient interface mount. The patient interface mountis attached to a mounting unit, which holds the focusing objective lens.This mounting unit is designed to ensure a stable connection between thepatient interface and the system in case of unavoidable movement of thepatient and allows gentler docking of the patient interface onto theeye. Various implementations for the focusing objective lens can beused. This presence of an adjustable focusing objective lens can changethe optical path length of the optical probe light as part of theoptical interferometer for the OCT sub-system. Movement of the objectivelens 5600 and patient interface 3300 can change the path lengthdifferences between the reference beam and the imaging signal beam ofthe OCT in an uncontrolled way and this may degrade the OCT depthinformation detected by the OCT. This would happen not only intime-domain but also in spectral/Fourier domain and frequency-swept OCTsystems.

FIGS. 7 and 8 show exemplary imaging-guided laser surgical systems thataddress the technical issue associated with the adjustable focusingobjective lens.

The system in FIG. 7 provides a position sensing device 7110 coupled tothe movable focusing objective lens 7100 to measure the position of theobjective lens 7100 on a slideable mount and communicates the measuredposition to a control module 7200 in the OCT system. The control system6100 can control and move the position of the objective lens 7100 toadjust the optical path length traveled by the imaging signal beam forthe OCT operation. A position encoder 7110 is coupled to the objectivelens 7100 and configured to measure a position change of the objectivelens 7100 relative to the applanation plate and the target tissue orrelative to the OCT device. The measured position of the lens 7100 isthen fed to the OCT control 7200. The control module 7200 in the OCTsystem applies an algorithm, when assembling a 3D image in processingthe OCT data, to compensate for differences between the reference armand the signal arm of the interferometer inside the OCT caused by themovement of the focusing objective lens 7100 relative to the patientinterface 3300. The proper amount of the change in the position of thelens 7100 computed by the OCT control module 7200 is sent to the control6100 which controls the lens 7100 to change its position.

FIG. 8 shows another exemplary system where the return mirror 6230 inthe reference arm of the interferometer of the OCT system or at leastone part in an optical path length delay assembly of the OCT system isrigidly attached to the movable focusing objective lens 7100 so thesignal arm and the reference arm undergo the same amount of change inthe optical path length when the objective lens 7100 moves. As such, themovement of the objective lens 7100 on the slide is automaticallycompensated for path-length differences in the OCT system withoutadditional need for a computational compensation.

The above examples for imaging-guided laser surgical systems, the lasersurgical system and the OCT system use different light sources. In aneven more complete integration between the laser surgical system and theOCT system, a femtosecond surgical laser as a light source for thesurgical laser beam can also be used as the light source for the OCTsystem.

FIG. 9 shows an example where a femtosecond pulse laser in a lightmodule 9100 is used to generate both the surgical laser beam forsurgical operations and the probe light beam for OCT imaging. A beamsplitter 9300 is provided to split the laser beam into a first beam asboth the surgical laser beam and the signal beam for the OCT and asecond beam as the reference beam for the OCT. The first beam isdirected through an x-y scanner 6410 which scans the beam in the x and ydirections perpendicular to the propagation direction of the first beamand a second scanner (z scanner) 6420 that changes the divergence of thebeam to adjust the focusing of the first beam at the target tissue 1001.This first beam performs the surgical operations at the target tissue1001 and a portion of this first beam is back scattered to the patientinterface and is collected by the objective lens as the signal beam forthe signal arm of the optical interferometer of the OCT system. Thisreturned light is combined with the second beam that is reflected by areturn mirror 6230 in the reference arm and is delayed by an adjustableoptical delay element 6220 for an time-domain OCT to control the pathdifference between the signal and reference beams in imaging differentdepths of the target tissue 1001. The control system 9200 controls thesystem operations.

Surgical practice on the cornea has shown that a pulse duration ofseveral hundred femtoseconds may be sufficient to achieve good surgicalperformance, while for OCT of a sufficient depth resolution broaderspectral bandwidth generated by shorter pulses, e.g., below several tensof femtoseconds, are needed. In this context, the design of the OCTdevice dictates the duration of the pulses from the femtosecond surgicallaser.

FIG. 10 shows another imaging-guided system that uses a single pulsedlaser 9100 to produce the surgical light and the imaging light. Anonlinear spectral broadening media 9400 is placed in the output opticalpath of the femtosecond pulsed laser to use an optical non-linearprocess such as white light generation or spectral broadening to broadenthe spectral bandwidth of the pulses from a laser source of relativelylonger pulses, several hundred femtoseconds normally used in surgery.The media 9400 can be a fiber-optic material, for example. The lightintensity requirements of the two systems are different and a mechanismto adjust beam intensities can be implemented to meet such requirementsin the two systems. For example, beam steering mirrors, beam shutters orattenuators can be provided in the optical paths of the two systems toproperly control the presence and intensity of the beam when taking anOCT image or performing surgery in order to protect the patient andsensitive instruments from excessive light intensity.

In operation, the above examples in FIGS. 2-10 can be used to performimaging-guided laser surgery. FIG. 11 shows one example of a method forperforming laser surgery by using an imaging-guided laser surgicalsystem. This method uses a patient interface in the system to engage toand to hold a target tissue under surgery in position and simultaneouslydirects a surgical laser beam of laser pulses from a laser in the systemand an optical probe beam from the OCT module in the system to thepatient interface into the target tissue. The surgical laser beam iscontrolled to perform laser surgery in the target tissue and the OCTmodule is operated to obtain OCT images inside the target tissue fromlight of the optical probe beam returning from the target tissue. Theposition information in the obtained OCT images is applied in focusingand scanning of the surgical laser beam to adjust the focusing andscanning of the surgical laser beam in the target tissue before orduring surgery.

FIG. 12 shows an example of an OCT image of an eye. The contactingsurface of the applanation lens in the patient interface can beconfigured to have a curvature that minimizes distortions or folds inthe cornea due to the pressure exerted on the eye during applanation.After the eye is successfully applanated at the patient interface, anOCT image can be obtained. As illustrated in FIG. 12, the curvature ofthe lens and cornea as well as the distances between the lens and corneaare identifiable in the OCT image. Subtler features such as theepithelium-cornea interface are detectable. Each of these identifiablefeatures may be used as an internal reference of the laser coordinateswith the eye. The coordinates of the cornea and lens can be digitizedusing well-established computer vision algorithms such as Edge or Blobdetection. Once the coordinates of the lens are established, they can beused to control the focusing and positioning of the surgical laser beamfor the surgery.

Alternatively, a calibration sample material may be used to form a 3-Darray of reference marks at locations with known position coordinates.The OCT image of the calibration sample material can be obtained toestablish a mapping relationship between the known position coordinatesof the reference marks and the OCT images of the reference marks in theobtained OCT image. This mapping relationship is stored as digitalcalibration data and is applied in controlling the focusing and scanningof the surgical laser beam during the surgery in the target tissue basedon the OCT images of the target tissue obtained during the surgery. TheOCT imaging system is used here as an example and this calibration canbe applied to images obtained via other imaging techniques.

In an imaging-guided laser surgical system described here, the surgicallaser can produce relatively high peak powers sufficient to drive strongfield/multi-photon ionization inside of the eye (i.e. inside of thecornea and lens) under high numerical aperture focusing. Under theseconditions, one pulse from the surgical laser generates a plasma withinthe focal volume. Cooling of the plasma results in a well defined damagezone or “bubble” that may be used as a reference point. The followingsections describe a calibration procedure for calibrating the surgicallaser against an OCT-based imaging system using the damage zones createdby the surgical laser.

Before surgery can be performed, the OCT is calibrated against thesurgical laser to establish a relative positioning relationship so thatthe surgical laser can be controlled in position at the target tissuewith respect to the position associated with images in the OCT image ofthe target tissue obtained by the OCT. One way for performing thiscalibration uses a pre-calibrated target or “phantom” which can bedamaged by the laser as well as imaged with the OCT. The phantom can befabricated from various materials such as a glass or hard plastic (e.g.PMMA) such that the material can permanently record optical damagecreated by the surgical laser. The phantom can also be selected to haveoptical or other properties (such as water content) that are similar tothe surgical target.

The phantom can be, e.g. a cylindrical material having a diameter of atleast 10 mm (or that of the scanning range of the delivery system) and acylindrical length of at least 10 mm long spanning the distance of theepithelium to the crystalline lens of the eye, or as long as thescanning depth of the surgical system. The upper surface of the phantomcan be curved to mate seamlessly with the patient interface or thephantom material may be compressible to allow full applanation. Thephantom may have a three dimensional grid such that both the laserposition (in x and y) and focus (z), as well as the OCT image can bereferenced against the phantom.

FIG. 13A-13D illustrate two exemplary configurations for the phantom.FIG. 13A illustrates a phantom that is segmented into thin disks. FIG.13 B shows a single disk patterned to have a grid of reference marks asa reference for determining the laser position across the phantom (i.e.the x- and y-coordinates). The z-coordinate (depth) can be determined byremoving an individual disk from the stack and imaging it under aconfocal microscope.

FIG. 13C illustrates a phantom that can be separated into two halves.Similar to the segmented phantom in FIG. 13A, this phantom is structuredto contain a grid of reference marks as a reference for determining thelaser position in the x- and y- coordinates. Depth information can beextracted by separating the phantom into the two halves and measuringthe distance between damage zones. The combined information can providethe parameters for image guided surgery.

FIG. 14 shows a surgical system part of the imaging-guided lasersurgical system. This system includes steering mirrors which may beactuated by actuators such as galvanometers or voice coils, an objectivelense and a disposable patient interface. The surgical laser beam isreflected from the steering mirrors through the objective lens. Theobjective lens focuses the beam just after the patient interface.Scanning in the x- and y-coordinates is performed by changing the angleof the beam relative to the objective lens. Scanning in z-plane isaccomplished by changing the divergence of the incoming beam using asystem of lens upstream to the steering mirrors.

In this example, the conical section of the disposable patient interfacemay be either air spaced or solid and the section interfacing with thepatient includes a curved contact lens. The curved contact lens can befabricated from fused silica or other material resistant to formingcolor centers when irradiated with ionizing radiation. The radius ofcurvature is on the upper limit of what is compatible with the eye,e.g., about 10 mm.

The first step in the calibration procedure is docking the patientinterface with the phantom. The curvature of the phantom matches thecurvature of the patient interface. After docking, the next step in theprocedure involves creating optical damage inside of the phantom toproduce the reference marks.

FIG. 15 shows examples of actual damage zones produced by a femtosecondlaser in glass. The separation between the damage zones is on average 8μm (the pulse energy is 2.2 μJ with duration of 580 fs at full width athalf maximum). The optical damage depicted in FIG. 15 shows that thedamage zones created by the femtosecond laser are well-defined anddiscrete. In the example shown, the damage zones have a diameter ofabout 2.5 μm. Optical damage zones similar to that shown in FIG. 14 arecreated in the phantom at various depths to form a 3-D array of thereference marks. These damage zones are referenced against thecalibrated phantom either by extracting the appropriate disks andimaging it under a confocal microscope (FIG. 13A) or by splitting thephantom into two halves and measuring the depth using a micrometer (FIG.13C). The x- and y- coordinates can be established from thepre-calibrated grid.

After damaging the phantom with the surgical laser, OCT on the phantomis performed. The OCT imaging system provides a 3D rendering of thephantom establishing a relationship between the OCT coordinate systemand the phantom. The damage zones are detectable with the imagingsystem. The OCT and laser may be cross-calibrated using the phantom'sinternal standard. After the OCT and the laser are referenced againsteach other, the phantom can be discarded.

Prior to surgery, the calibration can be verified. This verificationstep involves creating optical damage at various positions inside of asecond phantom. The optical damage should be intense enough such thatthe multiple damage zones which create a circular pattern can be imagedby the OCT. After the pattern is created, the second phantom is imagedwith the OCT. Comparison of the OCT image with the laser coordinatesprovides the final check of the system calibration prior to surgery.

Once the coordinates are fed into the laser, laser surgery can beperformed inside the eye. This involves photo-emulsification of the lensusing the laser, as well as other laser treatments to the eye. Thesurgery can be stopped at any time and the anterior segment of the eye(FIG. 11) can be re-imaged to monitor the progress of the surgery;moreover, after an intraocular lens (IOL) is inserted, imaging the IOL(with light or no applanation) provides information regarding theposition of the IOL in the eye. This information may be utilized by thephysician to refine the position of IOL.

FIG. 16 shows an example of the calibration process and thepost-calibration surgical operation. This examples illustrates a methodfor performing laser surgery by using an imaging-guided laser surgicalsystem can include using a patient interface in the system, that isengaged to hold a target tissue under surgery in position, to hold acalibration sample material during a calibration process beforeperforming a surgery; directing a surgical laser beam of laser pulsesfrom a laser in the system to the patient interface into the calibrationsample material to burn reference marks at selected three-dimensionalreference locations; directing an optical probe beam from an opticalcoherence tomography (OCT) module in the system to the patient interfaceinto the calibration sample material to capture OCT images of the burntreference marks; and establishing a relationship between positioningcoordinates of the OCT module and the burnt reference marks. After theestablishing the relationship, a patient interface in the system is usedto engage to and to hold a target tissue under surgery in position. Thesurgical laser beam of laser pulses and the optical probe beam aredirected to the patient interface into the target tissue. The surgicallaser beam is controlled to perform laser surgery in the target tissue.The OCT module is operated to obtain OCT images inside the target tissuefrom light of the optical probe beam returning from the target tissueand the position information in the obtained OCT images and theestablished relationship are applied in focusing and scanning of thesurgical laser beam to adjust the focusing and scanning of the surgicallaser beam in the target tissue during surgery. While such calibrationscan be performed immediately prior to laser surgery, they can also beperformed at various intervals before a procedure, using calibrationvalidations that demonstrated a lack of drift or change in calibrationduring such intervals.

The following examples describe imaging-guided laser surgical techniquesand systems that use images of laser-induced photodisruption byproductsfor alignment of the surgical laser beam.

FIGS. 17A and 17B illustrates another implementation of the presenttechnique in which actual photodisruption byproducts in the targettissue are used to guide further laser placement. A pulsed laser 1710,such as a femtosecond or picosecond laser, is used to produce a laserbeam 1712 with laser pulses to cause photodisruption in a target tissue1001. The target tissue 1001 may be a part of a body part 1700 of asubject, e.g., a portion of the lens of one eye. The laser beam 1712 isfocused and directed by an optics module for the laser 1710 to a targettissue position in the target tissue 1001 to achieve a certain surgicaleffect. The target surface is optically coupled to the laser opticsmodule by an applanation plate 1730 that transmits the laser wavelength,as well as image wavelengths from the target tissue. The applanationplate 1730 can be an applanation lens. An imaging device 1720 isprovided to collect reflected or scattered light or sound from thetarget tissue 1001 to capture images of the target tissue 1001 eitherbefore or after (or both) the applanation plate is applied. The capturedimaging data is then processed by the laser system control module todetermine the desired target tissue position. The laser system controlmodule moves or adjusts optical or laser elements based on standardoptical models to ensure that the center of photodisruption byproduct1702 overlaps with the target tissue position. This can be a dynamicalignment process where the images of the photodisruption byproduct 1702and the target tissue 1001 are continuously monitored during thesurgical process to ensure that the laser beam is properly positioned ateach target tissue position.

In one implementation, the laser system can be operated in two modes:first in a diagnostic mode in which the laser beam 1712 is initiallyaligned by using alignment laser pulses to create photodisruptionbyproduct 1702 for alignment and then in a surgical mode where surgicallaser pulses are generated to perform the actual surgical operation. Inboth modes, the images of the disruption byproduct 1702 and the targettissue 1001 are monitored to control the beam alignment. FIG. 17A showsthe diagnostic mode where the alignment laser pulses in the laser beam1712 may be set at a different energy level than the energy level of thesurgical laser pulses. For example, the alignment laser pulses may beless energetic than the surgical laser pulses but sufficient to causesignificant photodisruption in the tissue to capture the photodisruptionbyproduct 1702 at the imaging device 1720. The resolution of this coarsetargeting may not be sufficient to provide desired surgical effect.Based on the captured images, the laser beam 1712 can be alignedproperly. After this initial alignment, the laser 1710 can be controlledto produce the surgical laser pulses at a higher energy level to performthe surgery. Because the surgical laser pulses are at a different energylevel than the alignment laser pulses, the nonlinear effects in thetissue material in the photodisruption can cause the laser beam 1712 tobe focused at a different position from the beam position during thediagnostic mode. Therefore, the alignment achieved during the diagnosticmode is a coarse alignment and additional alignment can be furtherperformed to precisely position each surgical laser pulse during thesurgical mode when the surgical laser pulses perform the actual surgery.Referring to FIG. 17A, the imaging device 1720 captures the images fromthe target tissue 1001 during the surgical mode and the laser controlmodule adjust the laser beam 1712 to place the focus position 1714 ofthe laser beam 1712 onto the desired target tissue position in thetarget tissue 1001. This process is performed for each target tissueposition.

FIG. 18 shows one implementation of the laser alignment where the laserbeam is first approximately aimed at the target tissue and then theimage of the photodisruption byproduct is captured and used to align thelaser beam. The image of the target tissue of the body part as thetarget tissue and the image of a reference on the body part aremonitored to aim the pulsed laser beam at the target tissue. The imagesof photodisruption byproduct and the target tissue are used to adjustthe pulsed laser beam to overlap the location of the photodisruptionbyproduct with the target tissue.

FIG. 19 shows one implementation of the laser alignment method based onimaging photodisruption byproduct in the target tissue in laser surgery.In this method, a pulsed laser beam is aimed at a target tissue locationwithin target tissue to deliver a sequence of initial alignment laserpulses to the target tissue location. The images of the target tissuelocation and photodisruption byproduct caused by the initial alignmentlaser pulses are monitored to obtain a location of the photodisruptionbyproduct relative to the target tissue location. The location ofphotodisruption byproduct caused by surgical laser pulses at a surgicalpulse energy level different from the initial alignment laser pulses isdetermined when the pulsed laser beam of the surgical laser pulses isplaced at the target tissue location. The pulsed laser beam iscontrolled to carry surgical laser pulses at the surgical pulse energylevel. The position of the pulsed laser beam is adjusted at the surgicalpulse energy level to place the location of photodisruption byproduct atthe determined location. While monitoring images of the target tissueand the photodisruption byproduct, the position of the pulsed laser beamat the surgical pulse energy level is adjusted to place the location ofphotodisruption byproduct at a respective determined location whenmoving the pulsed laser beam to a new target tissue location within thetarget tissue.

FIG. 20 shows an exemplary laser surgical system based on the laseralignment using the image of the photodisruption byproduct. An opticsmodule 2010 is provided to focus and direct the laser beam to the targettissue 1700. The optics module 2010 can include one or more lenses andmay further include one or more reflectors. A control actuator isincluded in the optics module 2010 to adjust the focusing and the beamdirection in response to a beam control signal. A system control module2020 is provided to control both the pulsed laser 1010 via a lasercontrol signal and the optics module 2010 via the beam control signal.The system control module 2020 processes image data from the imagingdevice 2030 that includes the position offset information for thephotodisruption byproduct 1702 from the target tissue position in thetarget tissue 1700. Based on the information obtained from the image,the beam control signal is generated to control the optics module 2010which adjusts the laser beam. A digital processing unit is included inthe system control module 2020 to perform various data processing forthe laser alignment.

The imaging device 2030 can be implemented in various forms, includingan optical coherent tomography (OCT) device. In addition, an ultrasoundimaging device can also be used. The position of the laser focus ismoved so as to place it grossly located at the target at the resolutionof the imaging device. The error in the referencing of the laser focusto the target and possible non-linear optical effects such as selffocusing that make it difficult to accurately predict the location ofthe laser focus and subsequent photodisruption event. Variouscalibration methods, including the use of a model system or softwareprogram to predict focusing of the laser inside a material can be usedto get a coarse targeting of the laser within the imaged tissue. Theimaging of the target can be performed both before and after thephotodisruption. The position of the photodisruption by productsrelative to the target is used to shift the focal point of the laser tobetter localize the laser focus and photodisruption process at orrelative to the target. Thus the actual photodisruption event is used toprovide a precise targeting for the placement of subsequent surgicalpulses.

Photodisruption for targeting during the diagnostic mode can beperformed at a lower, higher or the same energy level that is requiredfor the later surgical processing in the surgical mode of the system. Acalibration may be used to correlate the localization of thephotodisruptive event performed at a different energy in diagnostic modewith the predicted localization at the surgical energy because theoptical pulse energy level can affect the exact location of thephotodisruptive event. Once this initial localization and alignment isperformed, a volume or pattern of laser pulses (or a single pulse) canbe delivered relative to this positioning. Additional sampling imagescan be made during the course of delivering the additional laser pulsesto ensure proper localization of the laser (the sampling images may beobtained with use of lower, higher or the same energy pulses). In oneimplementation, an ultrasound device is used to detect the cavitationbubble or shock wave or other photodisruption byproduct. Thelocalization of this can then be correlated with imaging of the target,obtained via ultrasound or other modality. In another embodiment, theimaging device is simply a biomicroscope or other optical visualizationof the photodisruption event by the operator, such as optical coherencetomography. With the initial observation, the laser focus is moved tothe desired target position, after which a pattern or volume of pulsesis delivered relative to this initial position.

As a specific example, a laser system for precise subsurfacephotodisruption can include means for generating laser pulses capable ofgenerating photodisruption at repetition rates of 100-1000 Millionpulses per second, means for coarsely focusing laser pulses to a targetbelow a surface using an image of the target and a calibration of thelaser focus to that image without creating a surgical effect, means fordetecting or visualizing below a surface to provide an image orvisualization of a target the adjacent space or material around thetarget and the byproducts of at least one photodisruptive event coarselylocalized near the target, means for correlating the position of thebyproducts of photodisruption with that of the sub surface target atleast once and moving the focus of the laser pulse to position thebyproducts of photodisruption at the sub surface target or at a relativeposition relative to the target, means for delivering a subsequent trainof at least one additional laser pulse in pattern relative to theposition indicated by the above fine correlation of the byproducts ofphotodisruption with that of the sub surface target, and means forcontinuing to monitor the photodisruptive events during placement of thesubsequent train of pulses to further fine tune the position of thesubsequent laser pulses relative to the same or revised target beingimaged.

The above techniques and systems can be used deliver high repetitionrate laser pulses to subsurface targets with a precision required forcontiguous pulse placement, as needed for cutting or volume disruptionapplications. This can be accomplished with or without the use of areference source on the surface of the target and can take into accountmovement of the target following applanation or during placement oflaser pulses.

While this document contains many specifics, these should not beconstrued as limitations on the scope of an invention or of what may beclaimed, but rather as descriptions of features specific to particularembodiments of the invention. Certain features that are described inthis document in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable subcombination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a subcombination or a variation of a subcombination.

A number of implementations of imaging-guided laser surgical techniques,apparatus and systems are disclosed. However, variations andenhancements of the described implementations, and other implementationscan be made based on what is described.

1. A laser surgical system, comprising: i. a pulse laser to produce alaser beam of laser pulses; ii. an optics module to receive the laserbeam and to focus and direct the laser beam onto a target tissue tocause photodisruption in the target tissue; iii. an applanation plateoperable to be in contact with the target tissue to produce an interfaceand to transmit laser pulses to the target and reflected or scatteredlight or sound from the target through the interface; iv. an imagingdevice to capture light or sound from the target to create an image ofthe target tissue; and v. a system control module to process imaginginformation on the image from the imaging device and to control theoptics module to adjust the laser beam focus to the target tissue basedon the imaging information.
 2. The system as in claim 1 wherein i. theimaging device captures an image of the target tissue and an image ofthe photodisruption byproduct generated in the target tissue by thephotodisruption; and ii. the system control module processes imaginginformation to obtain an offset in position between the image of thephotodisruption byproduct and a targeted position in the target tissue,wherein the system control module operates to control the optics moduleto adjust the laser beam to reduce the offset in subsequent laserpulses.
 3. The system as in claim 1, wherein the imaging device is anoptical coherence tomography (OCT) device or other optical imagingdevice.
 4. The system as in claim 1, wherein the imaging device createsan image of the target tissue after placement of the applanation plateon the surface of the target and before delivery by the pulse laser. 5.The system as in claim 4, wherein the imaging device creates an image ofthe target tissue at least one other time during the procedure to assessmovement of a subsurface target.
 6. The system as in claim 5, whereinmovement of the subsurface target during the procedure is caused byphotodisruptive byproducts comprising at least cavitation bubbles orshock waves.
 7. The system in claim 1, wherein the imaging device is anoptical coherence tomography (OCT) device positioned relative to theapplanation plate to have a known spatial relation with respect to theapplanation plate or the contacted surface of the target tissue, the OCTmodule configured to direct an optical probe beam to the target tissueand receive returned probe light of the optical probe beam from thetarget tissue through the applanation plate to capture OCT images of thetarget tissue before or while the surgical laser beam is being directedto the target tissue to perform an surgical operation so that theoptical probe beam and the surgical laser beam are sequentially orsimultaneously present in the target tissue, the OCT module incommunication with the laser control module to send information of thecaptured OCT images to the laser control module, wherein the lasercontrol module responds to the information of the captured OCT images tooperate the laser beam delivery module in focusing and scanning of thesurgical laser beam and adjusts the focusing and scanning of thesurgical laser beam in the target tissue based on positioninginformation in the captured OCT images.
 8. The system is claim 1,wherein the imaging device is an optical coherence tomography (OCT)device which is operable to suppress complex conjugates resulting fromthe optical configuration of the system or the presence of theapplanation plate.
 9. The system as in claim 1, wherein the imagingdevice is an optical coherence tomography (OCT) device configured tocapture OCT images of selected locations inside the target tissue toprovide three-dimensional positioning information for controllingfocusing and scanning of the surgical laser beam inside the targettissue.
 10. The system as in claim 1, wherein the imaging device is anoptical coherence tomography (OCT) device configured to capture OCTimages of selected locations on the surface of the target tissue or onthe applanation plate to provide positioning registration forcontrolling changes in orientation that occur with positional changes ofthe target, such as from upright to supine.
 11. The system as in claim10 wherein the positioning registration is performed via the placementof marks or markers in one positional orientation of the target that canthen be detected by the OCT module when the target is in anotherpositional orientation.
 12. The system as in claim 1, wherein theimaging device is an optical coherence tomography (OCT) device thatcomprises an OCT imaging module that is separate from the laser beamdelivery module and directs the optical probe beam to the target tissue.13. The system as in claim 1, wherein the imaging device is an opticalcoherence tomography (OCT) device to direct an optical probe beam to thetarget tissue to capture the image, and the system comprises a laserbeam delivery module comprising an objective lens module that directsboth the laser beam from the pulse laser and the optical probe beam fromthe OCT device to the applanation plate and the target tissue, as wellas returned probe light from the target tissue to the OCT device. 14.The system as in claim 1, wherein the imaging device is an opticalcoherence tomography (OCT) device to produce an optical probe beam tothe target tissue to capture the image, and the system comprises a laserbeam delivery module which comprises a surgical laser beam scannerlocated in an optical path of the laser beam to scan the surgical laserbeam without scanning the optical probe beam.
 15. The system as in claim1, wherein the imaging device is an optical coherence tomography (OCT)device to produce an optical probe beam to the target tissue to capturethe image, and the system comprises a laser beam delivery module whichcomprises a surgical laser beam scanner located in an optical path ofthe laser beam and an optical path of the optical probe beam to scanboth the surgical laser beam and the optical probe beam.
 16. The systemas in claim 1, wherein the imaging device is an optical coherencetomography (OCT) device to produce an optical probe beam to the targettissue to capture the image, and wherein the system comprises: anobjective lens module to focus the laser beam and the optical probe beamto the target tissue via the applanation plate; a position encodercoupled to the objective lens module and configured to measure aposition change of the objective lens module relative to the applanationplate and the target tissue or relative to the OCT device, wherein theOCT device comprises an optical reference path that receives a portionof the optical probe beam as a reference beam that is directed tospatially overlap with and to optically interfere with the returnedprobe light, and wherein the OCT device is in communication with theposition encoder to receive the measured position change of theobjective lens module and is configured to compensate for a change in anoptical path difference between the returned probe light and thereference beam caused by the position change of the objective lensmodule.
 17. The system as in claim 1, wherein the imaging device is anoptical coherence tomography (OCT) device to produce an optical probebeam to the target tissue to capture the image, and the OCT devicecomprises an optical reference path that receives a portion of theoptical probe beam as a reference beam, a reference mirror in theoptical reference path to reflect the reference beam that is directed tospatially overlap with and to optically interfere with the returnedprobe beam from the target tissue, and wherein the system comprises anobjective lens module to focus the laser beam and the optical probe beamto the target tissue via the applanation plate, and the reference mirroris coupled to the objective lens module to move with the objective lensmodule as the objective lens module is adjusted in position relative tothe applanation plate.
 18. The system as in claim 1, wherein the imagingdevice is an optical coherence tomography (OCT) device to produce anoptical probe beam to the target tissue to capture the image, andwherein the system comprises: a laser beam delivery module configured toreceive and direct both the laser beam and the optical probe beam toco-propagate along a common optical path to the applanation and thetarget tissue, wherein the OCT device receives returned probe light fromthe target tissue via the common optical path.
 19. The system as inclaim 18, wherein: the laser beam delivery module comprises a firstscanner in the common optical path to scan light in one or twodirections perpendicular to the common optical path, a second scanner inthe common optical path to change a divergence of light in the commonoptical path, and an objective lens module that directs light to andreceives returned light from the patient interface and the targettissue.
 20. The system as in claim 1, wherein the imaging device is anoptical coherence tomography (OCT) device to produce an optical probebeam to the target tissue to capture the image, wherein the systemcontrol module is configured to comprise OCT calibration data thatprovides a relationship between captured OCT images andthree-dimensional reference locations inside the target tissue, and thesystem control module is configured to apply the OCT calibration data infocusing and scanning of the laser beam during a surgery in the targettissue.
 21. The system as in claim 1, wherein the imaging device is anultrasound device.
 22. A method for targeting a pulsed laser beam to atarget tissue in laser surgery, comprising: i. monitoring image oftarget tissue of a body part and image of a reference on the body partto aim the pulsed laser beam at the target tissue; and ii. monitoringimages of photodisruption byproduct and the target tissue to adjust thepulsed laser beam to overlap the location of the photodisruptionbyproduct with the target tissue.
 23. The method as in claim 22, whereinthe reference on the body part is an applanation plate in contact withthe target tissue to produce an interface through which the pulsed laserbeam is directed to the target tissue.
 24. A method for targeting apulsed laser beam to a target tissue in laser surgery, comprising: i.monitoring image of target tissue of a body part and image of areference on the body part to aim the pulsed laser beam at the targettissue; ii. obtaining images of photodisruption byproduct in acalibration material to generate a three-dimensional reference systeminside the target tissue; and iii. controlling the focusing and scanningof the surgical laser beam during the surgery in the target tissue basedon the three-dimensional reference system.
 25. A method for targeting apulsed laser beam to a target tissue in laser surgery, comprising: i.aiming a pulsed laser beam at a target tissue location within targettissue to deliver a sequence of initial alignment laser pulses to thetarget tissue location; ii. monitoring images of the target tissuelocation and photodisruption byproduct caused by the initial alignmentlaser pulses to obtain a location of the photodisruption byproductrelative to the target tissue location; iii. controlling the pulsedlaser beam to carry surgical laser pulses at the surgical pulse energylevel; iv. adjusting a position of the pulsed laser beam at the surgicalpulse energy level to place the location of photodisruption byproduct atthe determined location; and v. while monitoring images of the targettissue and the photodisruption byproduct, continuing to adjust positionof the pulsed laser beam at the surgical pulse energy level to place thelocation of photodisruption byproduct at a respective determinedlocation when moving the pulsed laser beam to a new target tissuelocation within the target tissue.
 26. The method as in claim 25,wherein the location of photodisruption byproducts caused by surgicallaser pulses at a surgical pulse energy level is different from anenergy level of the initial alignment laser pulses used to initiallyplace the surgical pulses at the target tissue location.
 27. A lasersurgical system, comprising: i. a pulsed laser to produce a pulsed laserbeam; ii. a beam control optical module that directs the pulsed laserbeam at a target tissue location within target tissue to deliver asequence of initial alignment laser pulses to the target tissuelocation; iii. a monitor to monitor images of the target tissue locationand photodisruption byproduct caused by the initial alignment laserpulses to obtain a location of the photodisruption byproduct relative tothe target tissue location; and iv. a laser control unit that controls apower level of the pulsed laser beam to carry surgical laser pulses at asurgical pulse energy level different from the initial alignment laserpulses and operates the beam control optical module, based on monitoredimages of the target tissue and the photodisruption byproduct from themonitor, to adjust a position of the pulsed laser beam at the surgicalpulse energy level to place the location of photodisruption byproduct ata desired location.
 28. The system as in claim 27, comprising a curvedor flat applanation plate operable to be in contact with the targettissue to produce an interface, maintain hydration and optical qualityto transmit laser pulses to the target and returned light from thetarget through the interface.
 29. A method for performing laser surgeryby using an imaging-guided laser surgical system, comprising: using anapplanation plate in the system to engage to and to hold a target tissueunder surgery in position; sequentially or simultaneously directing asurgical laser beam of laser pulses from a laser in the system and anoptical probe beam from an optical coherence tomography (OCT) module inthe system to the patient interface into the target tissue; controllingthe surgical laser beam to perform laser surgery in the target tissue;operating the OCT module to obtain OCT images inside the target tissuefrom light of the optical probe beam returning from the target tissue;and applying position information in the obtained OCT images in focusingand scanning of the surgical laser beam to dynamically adjust thefocusing and scanning of the surgical laser beam in the target tissuebefore or during surgery.
 30. The method as in claim 29, comprising:directing both the surgical laser beam and the optical probe beam alonga common optical path to the patient interface and the target tissue.31. The method as in claim 29, comprising: operating a beam scanner inthe common optical path to scan both the surgical laser beam and theoptical probe beam to make the surgical laser beam trace a predeterminedsurgical pattern inside the target tissue.
 32. The method as in claim29, comprising: applying OCT calibration data, that provides arelationship between the obtained OCT images and three-dimensionalreference locations inside the target tissue, in controlling thefocusing and scanning of the surgical laser beam during the surgery inthe target tissue.
 33. A method for performing laser surgery by using animaging-guided laser surgical system, comprising: using an applanationplate in the system, to hold a calibration sample material during acalibration process before performing a surgery; directing a surgicallaser beam of laser pulses from a laser in the system to the patientinterface into the calibration sample material to burn reference marksat selected three dimensional reference locations; directing an opticalprobe beam from an optical coherence tomography (OCT) module in thesystem to the patient interface into the calibration sample material tocapture OCT images of the burnt reference marks; establishing arelationship between positioning coordinates of the OCT module and theburnt reference marks; after the establishing the relationship, using apatient interface in the system to engage to and to hold a target tissueunder surgery in position; simultaneously or sequentially directing thesurgical laser beam of laser pulses and the optical probe beam to thepatient interface into the target tissue; controlling the surgical laserbeam to perform laser surgery in the target tissue; operating the OCTmodule to obtain OCT images inside the target tissue from light of theoptical probe beam returning from the target tissue; and applyingposition information in the obtained OCT images and the establishedrelationship in focusing and scanning of the surgical laser beam todynamically adjust the focusing and scanning of the surgical laser beamin the target tissue before or during surgery.
 34. A laser system forperforming laser surgery on the eye, comprising: a control system; alaser source emitting a laser beam for surgically affecting the tissueof an eye under a control of the control system; an optical coherencetomography (OCT) imaging system a control of the control system toproduce a probe light beam that optically gathers information on aninternal structure of the eye; an attachment mechanism structured to fixthe surface of the eye in position and to provide reference in threedimensional space relative to the OCT imaging system; a mechanism tosupply the control system with positional information on the internalstructure of the eye derived from the OCT imaging system; and an opticalunit that focuses the laser beam controlled by the control system intothe eye for surgical treatment.
 35. The system as in claim 34, wherein:the attachment mechanism comprises a flat or curved lens contacting theanterior surface of the eye to maintain surface hydration, maintainoptical quality.
 36. The system as in claim 34, wherein: the lasersource is a pulsed laser emitting pulses of duration ranging from 1femtosecond to 100 picoseconds.
 37. The system as in claim 34, wherein:the OCT imaging system comprises a time-domain OCT imaging system or aspectral domain OCT imaging system.
 38. The system as in claim 34,wherein: the OCT imaging system comprises a femtosecond laser source ora low coherent length superluminescent diode to produce an optical probebeam to the eye.
 39. The system as in claim 34, wherein: the OCT imagingsystem comprises a frequency-swept light source to produce an opticalprobe beam to the eye.
 40. The system as in claim 34, comprising: acommon focusing objective lens positioned relative to the attachmentmechanism to focus the laser beam and the probe light beam to the eye toacquire optical coherence tomographic information on the internalstructure of the eye.
 41. The system as in claim 40, wherein: theinternal structure of the eye includes at least a portion of thecrystalline lens of the eye and or cornea.
 42. The system as in claim40, comprising: a common scanning mechanism to scan both the laser beamperpendicular to the optical axis for surgically affecting the tissue ofthe eye and the probe light for acquiring a cross section perpendicularto the optical axis of an optical coherence tomographic image.
 43. Thesystem as in claim 40, comprising: an optical beam combining device tocombine at least the laser beam and the probe light into a combined beamand to direct the combined beam to the common focusing objective lens.44. The system as in claim 43, wherein: the optical beam combiningdevice comprises at least one of or a combination of an optical beamsplitter, a dichroic beam splitter, a polarization beam splitter, anoptical grating, a fiber-optic beam splitter and a holographic beamsplitter.
 45. The system as in claim 34, wherein: the OCT imaging systemproduces a probe light beam that is polarized to optically gather theinformation on the internal structure of the eye.
 46. The system as inclaim 45, wherein: the laser beam and the probe light beam are polarizedin different polarizations.
 47. The system as in claim 34, comprising: apolarization control mechanism that controls the probe light to polarizein one polarization when traveling toward the eye and in a differentpolarization when traveling away from the eye.
 48. The system as inclaim 47 wherein: the polarization control mechanism comprises awaveplate.
 49. The system as in claim 47, wherein: the polarizationcontrol mechanism comprises a Faraday rotator.
 50. The system as inclaim 34, wherein: the probe light beam in the OCT imaging system is abeam split from the laser beam for surgically affecting the tissue ofthe eye.
 51. The system as in claim 34, wherein: the probe light beam inthe OCT imaging system is a beam produced by white-light generationusing the laser beam for surgically affecting the tissue of the eye. 52.The system as in claim 34, wherein: the laser beam and the probe lightbeam are in two different spectral bands that overlap with each other.53. The system as in claim 34, comprising: a first scanning mechanismscanning a focus of the laser beam along the propagation direction ofthe laser beam to surgically affect the tissue of the eye at varyingdepths; and a second scanning mechanism scanning a reference arm delayinside the OCT imaging system, wherein the first and second scanningmechanisms are synchronized to each other.
 54. The system as in claim34, comprising: a common focusing objective lens positioned relative tothe attachment mechanism to focus the laser beam and the probe lightbeam to the eye; a lens base to which the common focusing objective lensis slidably mounted; a measuring device that measures a position of thecommon focusing objective lens relative to the lens base; and a signalcommunication mechanism to communicate the measured position to the OCTimaging system to compensate for path-length differences between asignal arm and a reference arm of an interferometer of the OCT imagingsystem.
 55. The system as in claim 34, comprising: a common focusingobjective lens positioned relative to the attachment mechanism to focusthe laser beam and the probe light beam to the eye; a lens base to whichthe common focusing objective lens is slidably mounted; and wherein theOCT imaging system comprises a return mirror in a reference arm of anoptical interferometer in the OCT imaging system, and the return mirroris rigidly attached to the common focusing objective lens.
 56. Thesystem as in claim 34, comprising: a common focusing objective lenspositioned relative to the attachment mechanism to focus the laser beamand the probe light beam to the eye; a lens base to which the commonfocusing objective lens is slidably mounted; and wherein the OCT imagingsystem comprises a path-length delay assembly in a reference arm of anoptical interferometer in the OCT imaging system and at least one partof the path-length delay assembly is rigidly attached to the commonfocusing objective lens.
 57. The system as in 56, wherein: the opticalinterferometer in the OCT imaging system is rigidly attached to theslidable lens
 58. An imaging-guided laser surgical system, comprising: asurgical laser that produces a surgical laser beam of surgical laserpulses that cause surgical changes in a target tissue under surgery; apatient interface mount that engages a patient interface in contact withthe target tissue to hold the target tissue in position; a laser beamdelivery module located between the surgical laser and the patientinterface and configured to direct the surgical laser beam to the targettissue through the patient interface, the laser beam delivery moduleoperable to scan the surgical laser beam in the target tissue along apredetermined surgical pattern; a laser control module that controlsoperation of the surgical laser and controls the laser beam deliverymodule to produce the predetermined surgical pattern; and an opticalcoherence tomography (OCT) module positioned relative to the patientinterface to have a known spatial relation with respect to the patientinterface and the target issue fixed to the patient interface, the OCTmodule configured to direct an optical probe beam to the target tissueand receive returned probe light of the optical probe beam from thetarget tissue to capture OCT images of the target tissue while thesurgical laser beam is being directed to the target tissue to perform ansurgical operation so that the optical probe beam and the surgical laserbeam are simultaneously present in the target tissue, the OCT module incommunication with the laser control module to send information of thecaptured OCT images to the laser control module, wherein the lasercontrol module responds to the information of the captured OCT images tooperate the laser beam delivery module in focusing and scanning of thesurgical laser beam and adjusts the focusing and scanning of thesurgical laser beam in the target tissue based on positioninginformation in the captured OCT images.
 59. The system as in claim 58,wherein: the OCT module is configured to capture OCT images of selectedlocations inside the target tissue to provide three-dimensionalpositioning information for controlling focusing and scanning of thesurgical laser beam inside the target tissue.
 60. The system as in claim58, wherein: the OCT module comprises an OCT imaging module that isseparate from the laser beam delivery module and directs the opticalprobe beam to the target tissue.
 61. The system as in claim 58, wherein:the laser beam delivery module comprises an objective lens module thatdirects both the surgical laser beam from the surgical laser and theoptical probe beam from the OCT module to the patient interface and thetarget tissue.
 62. The system as in claim 61, wherein: the laser beamdelivery module comprises a surgical laser beam scanner located in anoptical path of the surgical laser beam to scan the surgical laser beamwithout scanning the optical probe beam.
 63. The system as in claim 61,wherein: the laser beam delivery module comprises a surgical laser beamscanner located in an optical path of the surgical laser beam and anoptical path of the optical probe beam to scan both the surgical laserbeam and the optical probe beam.
 64. The system as in claim 61,comprising: a position encoder coupled to the objective lens module andconfigured to measure a position change of the objective lens modulerelative to the patient interface and the target tissue, wherein the OCTmodule comprises an optical reference path that receives a portion ofthe optical probe beam as a reference beam that is directed to spatiallyoverlap with and to optically interfere with the returned probe light,and wherein the OCT module is in communication with the position encoderto receive the measured position change of the objective lens module andis configured to compensate for a change in an optical path differencebetween the returned probe light and the reference beam caused by theposition change of the objective lens module.
 65. The system as in claim61, wherein: the OCT module comprises an optical reference path thatreceives a portion of the optical probe beam as a reference beam, andthe optical reference path comprises a reference mirror to reflect thereference beam that is directed to spatially overlap with and tooptically interfere with the returned probe light, and wherein thereference mirror is coupled to the objective lens module to move withthe objective lens module as the objective lens module is adjusted inposition relative to the patient interface.
 66. The system as in claim58, wherein: the laser beam deliver module is configured to receive anddirect both the surgical laser beam and the optical probe beam toco-propagate along a common optical path to the patient interface andthe target tissue, and the OCT module receives the returned probe lightfrom the target tissue via the common optical path.
 67. The system as inclaim 66, wherein: the laser beam delivery module comprises a firstscanner in the common optical path to scan light in one or twodirections perpendicular to the common optical path, a second scanner inthe common optical path to change a divergence of light in the commonoptical path, and an objective lens module that directs light to andreceives returned light from the patient interface and the targettissue.
 68. The system as in claim 58, wherein: the laser control moduleis configured to comprise OCT calibration data that provides arelationship between the captured OCT images and three-dimensionalreference locations inside the target tissue, and the laser controlmodule is configured to apply the OCT calibration data in focusing andscanning of the surgical laser beam during a surgery in the targettissue.